High Concentration of Epigallocatechin-3-Gallate Increased the Incidences of Arrhythmia and Diastolic Dysfunction Via β2-adrenoceptor

Epigallocatechin-3-gallate (EGCG) is the major and most potent representative in green tea, which has been proved to modulate myocardial contractility. Whether EGCG has some negative effects on cardiac function is not known. In the present study, we investigated the effects of EGCG at different doses on cardiac contraction and explored whether beta 2-adrenoceptor (beta 2AR) was involved in EGCG-induced cardiac effects. Isolated rat hearts were mounted on the Langendorff system and perfused with different concentrations of EGCG in low or normal calcium Krebs-Henseleit (KH) buffer. The contraction of hearts was measured. Ventricular myocytes were cultured with EGCG and isoprenaline (ISO, 10(-7) M) for 12 h. ICI118,551 (55 nM) was used to inhibit beta(2)AR. Cardiomyocyte shortening, viability, and responsiveness to ISO (10(-9) M) were measured. EGCG dose dependently enhanced contractility of perfused heart in low calcium KH buffer. In the normal calcium KH buffer, EGCG at low dose (20 mu M) increased heart contraction, while at high dose (50 mu M), it increased the incidences of arrhythmia and diastolic dysfunction. In isolated ventricular myocytes, EGCG at the concentration of 0.001 to 1.0 mu M did not affect their contraction. However, the responsiveness to ISO and the survival of myocytes were increased by EGCG (0.01 mu M). The increased responsiveness was partially abolished by ICI118,551. The data obtained in this study demonstrated that EGCG at low dose conferred cardioprotection, yet at high dose increased the incidences of arrhythmia and diastolic dysfunction. beta(2)AR was involved in EGCG-induced cardiac effects.